Recruiting

Phase 2

Obeticholic AcidObeticholic Acid for Prevention in Barrett's Esophagus

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04939051

Conditions

Barrett Esophagus

Esophageal Adenocarcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Esophageal Biopsy

Esophagogastroduodenoscopy

Liver Ultrasonographic Elastography

Obeticholic Acid

Study Details

Brief summary:

This phase II trial studies the effect of obeticholic acid in treating patients with Barrett's esophagus. Bile acids present in duodenogastroesophageal reflux contribute to neoplastic progression in Barrett's esophagus. Obeticholic acid has shown anti-cholestatic, anti-inflammatory and anti-fibrotic effects mediated by FXR activation. It down regulates bile acid availability and decreases proinflammatory cytokine production including IL-1beta and TNFalpha in human enterocytes and immune cells. This chain of events reduces the bile acid exposure in esophagus tissue thereby limiting bile acid induced damage and dysplastic progression.

Conditions

Barrett Esophagus

Esophageal Adenocarcinoma

Study ID

NCT04939051

Start date

Jan 3, 2024

Status verified date

Jul, 2026

Completion date

Sep 1, 2027

Anticipated

Primary completion date

Sep 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Known diagnosis of histologically-confirmed BE with either no dysplasia, indefinite for dysplasia, or low-grade dysplasia as defined by the presence of specialized columnar epithelium on histology and >= 2 cm of involvement on endoscopy
Adequate Barrett's mucosa, which is defined as at least one sample with >= 50% intestinal metaplasia in biopsies required to satisfy the endpoints of the study
Participants are on proton pump inhibitors (PPI) therapy for >= 28 days duration
Age >= of 18 years. Because no dosing or adverse event (AE) data are currently available on the use of OCA in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
Hemoglobin >= 10g/dL or hematocrit >= 30 %
Leukocyte count >= 3,500/microliter
Platelet count >= 100,000/microliter
Creatinine clearance (calculated if measured is not available) >= 30mL/min/1.73m\^2
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 1.5 X institutional upper limit of normal (ULN)
Total bilirubin =< 1.0 X ULN
Alkaline phosphatase =<1.5 X ULN
Gamma-glutamyl transferase (GGT) =< 1.5 X ULN
The effects of OCA on the developing human fetus are unknown. For this reason, all men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of study participation, and for at least 6 months after receiving the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Ability to understand the study procedures, benefits and risks, and sign a written informed consent document. Non-English speaking participants are allowed to enroll even if they skip answering quality-of-life (QOL) questionnaires. Special efforts will be made through community advisory boards at participating sites to reach Spanish speaking participants
Willing to undergo testing for human immunodeficiency virus (HIV) testing if not tested within the past 6 months
Willing to undergo hepatitis B and C screening if not tested within the past 6 months
Willing and able to adhere to the prohibitions and restrictions specified in the approved protocol
Willingness to moderate alcohol intake (consuming no more than 1 or 2 alcoholic drinks per day for women and men, respectively)
Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)

Exclusion Criteria:

History of prior ablative therapy such as radiofrequency ablation, cryotherapy or argon plasma coagulation (APC) in BE segment
Prior use of OCA
Prior history or presence of high-grade disease (HGD) or cancer on pre-intervention endoscopy
Cutaneous diseases manifesting with severe pruritus
Individuals with active, known or suspected chronic liver disease including cirrhosis, nonalcoholic steatohepatitis (NASH) with fibrosis or cirrhosis, primary sclerosing cholangitis, biliary atresia
Individuals with acute cholecystitis (defined by a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation)
Individuals with a history of pancreatitis or pancreatic abnormalities
Individuals with hepatic steatosis and velocity > 1.7 m/sec as determined by liver ultrasound elastography. Results of a right upper quadrant ultrasound with elastography performed within 6 months of starting study treatment may be used to assess this criteria
Individuals with hyperlipidemia that is not well controlled with the use of pharmacotherapy and/or dietary modifications
History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
Individuals with known hypersensitivity, allergies, or intolerance to the study drug or compounds of similar chemical or biologic composition
Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Individuals with active and untreated hepatitis C virus (HCV) and/or or hepatitis B virus (HBV) infection
Individuals with HIV infection are eligible for participation if:

CD4+ count >= 300/uL
Viral load is undetectable
Receiving highly active antiretroviral therapy (HAART) without known or suspected drug interactions with OCA
Consultation with the participant's infectious disease specialist may be obtained
Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 5 half-lives days prior to starting OCA or placebo on this study. Consultation with the participant's primary care provider may be obtained but is not required.

The use of the following drugs or drug classes is prohibited during OCA/placebo treatment

Investigational agents;
Bile acid sequestrants (bile acid binding resins): cholestyramine, colestipol, or colesevelam;
Bile salt efflux pump (BSEP) inhibitors;
Clozapine;
Theophylline derivatives;
Tizanidine;
Warfarin;
Hepatotoxic drugs such as amiodarone, sodium valproate, certain herbal/dietary supplements, and long-term doxycycline or tetracycline
Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contraceptive method. Pregnant women are excluded from this study because OCA is an agent with unknown effects on the developing human fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA
Participants may not be receiving any other investigational agents

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Arm I (OCA)

Patients receive OCA PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound with elastography during screening, EGD with biopsies, brushings and gastric aspirate at screening and end of treatment visit and blood sample collection throughout the study.

placebo comparator: Arm II (placebo)

Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound with elastography during screening, EGD with biopsies, brushings and gastric aspirate at screening and end of treatment visit and blood sample collection throughout the study.

Interventions

Biospecimen Collection

Undergo blood sample collection

Esophageal Biopsy

Undergo esophageal biopsy, brushings and gastric aspirate

Esophagogastroduodenoscopy

Undergo EGD

Liver Ultrasonographic Elastography

Undergo liver ultrasound with elastography

Obeticholic Acid

Given PO

Placebo Administration

Given PO

Questionnaire Administration

Ancillary study

Primary outcome measure

Mean change in leucine-rich repeat-containing G-protein coupled receptor 5+ cell count [ Time Frame: Baseline up to 6 months ]

Central Contacts and Locations

Locations

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Ajay Bansal

816-861-4700 abansal@kumc.edu

Principal Investigator:

Ajay Bansal

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Scott M. Schuetze

734-647-8925 scotschu@med.umich.edu

Principal Investigator:

Scott M. Schuetze

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Dayna S. Early

314-454-5960 dearly@wustl.edu

Principal Investigator:

Dayna S. Early

UNC Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Nicholas J. Shaheen

919-966-7047 nshaheen@med.unc.edu

Principal Investigator:

Nicholas J. Shaheen

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Amitabh Chak

216-844-7344 amitabh.chak@uhhospitals.org

Principal Investigator:

Amitabh Chak

Cleveland Clinic Foundation

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Prashanthi Thota

216-444-0780 thotap@ccf.org

Principal Investigator:

Prashanthi Thota

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 11, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-11.